This project is aimed at a concerted effort to investigate the biology, biochemistry and pathology of connective tissues. Studies are to be conducted on the chemical structure of certain glycosaminoglycans with particular emphasis on heparin, heparan sulfate and keratan sulfate. Continuing studies are being carried out on the pathways of biosynthesis of glycosaminoglycans including the localization within cells and the mechanism of control of these biosynthetic reactions. The interactions of proteoglycans with collagen are being investigated with a view to elucidating the biological action of proteoglycans. Differentiation of chondrocytes in tissue culture is being studied. Fibroblasts of human genetic diseases of connective tissue are being studied for purposes of elucidating the gene product defects in mucopolysaccharidoses and glycosphingolysidoses. Products prepared by the chemical modification of heparin are being studied for their ability to prevent dietary-induced atherosclerosis. The synthesis of glycosaminoglycans by cultured glial cells and neuroblastoma cells is also being studied.